citrullinemia, type II, adult-onset

Adult-onset citrullinemia type II is an inherited metabolic disorder that primarily affects the liver and nervous system, leading to the accumulation of ammonia and other toxic substances in the blood. The condition is caused by mutations in the SLC25A13 gene and typically presents during adulthood, sometimes in individuals who had neonatal intrahepatic cholestasis due to citrin deficiency (NICCD) that resolved in infancy. Although precise prevalence estimates are not well established, the disorder is recognized as uncommon and requires careful management given the potential for life-threatening complications. Clinical symptoms are often triggered by factors such as certain medications, infections, surgery, or alcohol intake.

Individuals with adult-onset citrullinemia type II may experience a range of neurological and hepatic manifestations. Characteristic features include elevated plasma citrulline levels, which are always present, along with laboratory evidence of liver dysfunction such as elevated alanine aminotransferase and hepatic steatosis. Neurological symptoms can involve confusion, restlessness, memory loss, and abnormal behaviors like aggression, irritability, and hyperactivity. In more severe cases, patients may suffer from seizures, coma, and other complications such as pancreatitis. Not all individuals experience all features, and severity varies considerably.

Adult-onset citrullinemia type II is caused by pathogenic variants in the SLC25A13 gene. This gene is responsible for encoding a protein crucial to the proper transport of metabolites within liver cells, and mutations disrupt its normal function, leading to the accumulation of ammonia and other toxic substances. The condition is inherited in an autosomal recessive pattern, meaning that an individual must inherit two altered copies of the gene—one from each parent—to be affected. Families with shared ancestry may have a higher chance of both parents being carriers, which underscores the importance of genetic counseling for family planning.

Currently, management of adult-onset citrullinemia type II focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. Treatment is tailored to the individual's needs and generally involves a multidisciplinary team that may include specialists in metabolic disorders, neurology, and hepatology. Regular monitoring of liver function and neurological status is important, and patients are encouraged to discuss treatment options with their healthcare team. Genetic counseling is also recommended to help families understand the implications of the autosomal recessive inheritance pattern.

The clinical course of adult-onset citrullinemia type II is highly variable, with outcomes depending on factors such as the severity of symptoms, age at diagnosis, and access to specialized care. While some individuals may experience severe episodes including seizures and coma, others have a more moderate presentation with periods of relative stability. With current standards of care, many patients are able to manage their symptoms and maintain quality of life, although complications can be life-threatening. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with genetic counselors and specialized care centers for ongoing support and guidance.

There are a few clinical trials currently underway exploring new treatment approaches for adult-onset citrullinemia type II. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team to learn more about eligibility and potential participation.